JPET xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Burton, C. K.
Right arrow Articles by Hoskins, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Burton, C. K.
Right arrow Articles by Hoskins, B.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*MORPHINE

Evidence for involvement of cyclic GMP phosphodiesterase in morphine tolerance

CK Burton, IK Ho and B Hoskins

Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson.

Preliminary evidence had suggested that changes in cyclic GMP (cGMP) hydrolysis via cyclic nucleotide phosphodiesterase(s) occurred during development of tolerance to morphine. To examine this finding further and its possible role in development of tolerance to morphine, rats (150-175 g) were injected with 1 ml of a sustained-release morphine preparation (40 mg/ml). Control rats received 1 ml of the oily vehicle. Antinociception, decreased locomotor activity, respiratory depression and mydriasis were measured at various times from 0.5 through 96 hr of exposure to the drug. Particulate and soluble cGMP hydrolysis were measured for the same time periods from periaqueductal gray (PAG), striatum, medulla and oculomotor nucleus, the brain areas believed to mediate the respective behaviors. Each of the behaviors except mydriasis showed development of complete tolerance (no difference from control behaviors) during the 96 hr of continuous exposure. During development of tolerance, particulate cGMP hydrolysis decreased in PAG and increased in striatum and medulla. Particulate cGMP hydrolysis was not altered in oculomotor nucleus, the brain area mediating mydriasis to which tolerance development was partial or incomplete. Significant changes in soluble cGMP hydrolysis occurred only in PAG before decline in the behavioral effect and did not appear to be involved in tolerance phenomena. Modulation of cyclic nucleotide levels by changes in particulate cGMP hydrolysis may produce or allow for development of complete tolerance to various morphine-induced behaviors.

Volume 252, Issue 1, pp. 104-111, 01/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
B. Kest, G. McLemore, B. Kao, and C. E. Inturrisi
The Competitive alpha -Amino-3-Hydroxy-5-Methylisoxazole-4-Propionate Receptor Antagonist LY293558 Attenuates and Reverses Analgesic Tolerance to Morphine But Not to Delta or Kappa Opioids
J. Pharmacol. Exp. Ther., December 1, 1997; 283(3): 1249 - 1255.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1990 by the American Society for Pharmacology and Experimental Therapeutics.